Age-related changes of A1 and A2a adenosine receptor binding characteristics were investigated in three regions of the rat brain using the A1 selective antagonist [3H]DPCPX, and the A2a selective agonist [3H]CGS 21680. The density of A1 binding sites in aged rats (24 months) was decreased by 33% in the hippocampus and by 60% in the cortex and was unchanged in the striatum when compared with young adult rats (6 weeks), with no change in KD. There were also age-related changes in the density of A2a binding sites: in the cortex, there was a 94% increase in the number of [3H]CGS 21680 binding sites in aged rats compared with young rats, and a similar tendency was observed in the hippocampus (32% increase in A2a binding sites in aged rats), with no change in KD; in the striatum there was a tendency for a decrease (22%) in the number of [3H]CGS 21680 binding sites in aged rats, and a decrease in KD. These results suggest that there are age-related changes in the balance between inhibitory A1- and excitatory A2a-adenosine receptor-mediated actions, which vary in different brain areas: in the cortex and hippocampus, the balance might be shifted towards adenosine-mediated excitatory actions, since there is an increase in the number of A2a receptors and a decrease in the number of A1 receptors upon ageing. In contrast, in the striatum, the A1/A2a ratio might be only slightly affected upon ageing.